P1035: RING SIDEROBLASTS &lt;15% WAS AN INDEPENDENT RISK FACTOR FOR MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASM WITH SF3B1 MUTATION AND THROMBOCYTOSIS
Authors: Fuhui LI, Zhijian Xiao, Zefeng Xu
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: The 5th edition of the World Health Organization (WHO) classification of myeloid neoplasms put forward the definition of myelodysplastic/myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis (MDS/MPN-SF3B1-T) which was characterized by SF3B1 mutation, ring sideroblasts (RS) and thrombocytosis. Thus, patients with SF3B1 mutation and <15% bone marrow (BM) RS were newly included in the disease entity. However, there were few clinical studies related to MDS/MPN-SF3B1-T, especially those with <15% RS until now. Aims: We described the mutational landscape of patients diagnosed MDS/MPN-SF3B1-T and compared clinical features, gene alterations and overall survival (OS) of patients with ≥15% BM RS and <15% BM RS. In addition, we explored independent risk factors for prognosis of patients with MDS/MPN-SF3B1-T. Methods: A total of 179 patients diagnosed MDS/MPN-SF3B1-T based on 2022 (5th edition) WHO classification of myeloid neoplasms from our center from June 2006 to November 2022 were included in the study. The data of clinical features, gene alterations and survival were retrospectively analyzed. Survivals of different subgroups were analyzed by the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazard regression model was used for multivariable analysis to evaluate independent prognostic factors of patients with MDS/MPN-SF3B1-T. Results: 136 patients of our cohort harbored SF3B1 mutations, 114 with ≥15% BM RS and 22 with <15% BM RS, and remaining 43 patients whose SF3B1 mutations were negative or unavailable owned ≥15% BM RS. Among 179 patients with MDS/MPN-SF3B1-T, 124 were tested Next-generation-sequencing (NGS). Common gene mutations encountered in patients with MDS/MPN-SF3B1-T include SF3B1 (93.5%), JAK2 (29.8%), TET2 (19.4%), DNMT3A (12.9%), ASXL1 (11.3%), MPL（4.8%）, TP53 (5.6%), SETBP1（4.8%）and 33.1% harbored both the SF3B1 and myeloproliferative neoplasm (MPN)-restricted driver mutation (Figure 1). The median OS of patients with <15% BM RS (n=22) and ≥15% BM RS (n=157) was 36 and 80 months respectively, which was significantly different (P<0.001) (Figure 2). The percentage of male patients (81.8% vs 57.3%, P=0.028), serum lactate dehydrogenase (LDH) (302.5U/L vs 194.2U/L, P=0.001), BM blasts（1.5% vs 0.5%, P=0.040）and the percentage of TP53 mutation (19% vs 2.9%, P=0.016) were significantly different between subgroups of patients with <15% RS and ≥15% RS (Table 1). Multivariable Cox regression analysis indicated that age≥65 years [P=0.004, hazard ratio (HR) 2.714, 95% confidence interval (CI) 1.384~5.322], hemoglobin (Hb) level<80g/L (P=0.011, HR 2.338, 95%CI 1.213~4.506), complex karyotype (P=0.024, HR 5.829, 95%CI 1.266~26.834), BM blasts≥0.5% (P=0.044, HR 1.857, 95%CI 1.016~3.394) and BM RS<15% (P=0.002, HR 3.447, 95%CI 1.577~7.534) were independent risk factors for OS of patients with MDS/MPN-SF3B1-T. Summary/Conclusion: Our results showed that RS<15% was an independent risk factor for patients with MDS/MPN-SF3B1-T. RS<15% may become a factor to define subtypes with separate prognosis in patients with MDS/MPN-SF3B1-T.Keywords: Thrombocytosis, Myelodysplasia, Survival prediction, Anemia